SARS-COV-2 VARIANTS OF CONCERN AND VARIANTS UNDER INVESTIGATION IN ENGLAND - TECHNICAL BRIEFING 34 - GOV.UK
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SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 34 14 January 2022 This report provides an update on previous briefings up to 31 December 2021
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Contents
Summary...................................................................................................................................... 3
Published information on variants ................................................................................................ 5
Part 1. Surveillance overview ....................................................................................................... 6
1.1 VOC and VUI overview ....................................................................................................... 6
1.2 Variant prevalence.............................................................................................................. 6
Part 2. Enhanced analyses of Omicron VOC-21NOV-01 (B.1.1.529) ........................................ 14
2.1 Genomic diversity ............................................................................................................. 14
2.2 Severity and hospitalisation .............................................................................................. 20
2.4 Symptom comparison of Omicron and Delta cases in England ........................................ 21
2.5 Vaccine effectiveness ....................................................................................................... 24
2.6 Update on the SARS-CoV-2 Immunity and Reinfection Evaluation in healthcare workers
(SIREN) study ........................................................................................................................ 28
2.7 Reinfections ...................................................................................................................... 32
Sources and acknowledgments ................................................................................................. 37
Data sources .......................................................................................................................... 37
Repository of human and machine-readable genomic case definitions .................................. 37
Authors of this report .............................................................................................................. 37
Acknowledgements ................................................................................................................ 39
2
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Summary
This report has been published to share the detailed variant surveillance analyses which
contribute to the variant risk assessments and designation of new variants of concern (VOC)
and variants under investigation (VUI). This specialist technical briefing contains early data and
analysis on emerging variants and findings have a high level of uncertainty.
SARS-CoV-2 Routine variant data update covers surveillance data and sequencing coverage
data on all other VOCs and VUIs. Unless stated otherwise, this technical briefing uses a data
cut-off of 10 January 2022 to allow time for analyses. In summary:
Genomic diversity
There is as yet little diversity within the Omicron BA.1 clade. Two acquired mutations in spike
have been noted in the UK data set, A701V and R346K. The growth rate of Omicron with these
mutations is not greater than the rest of the Omicron clade.
Omicron also contains the clade BA.2. This is being separately monitored and assessed from a
technical perspective and is included in overall Omicron case counts.
Severity
There is no update on the overall severity analysis this week. A rise in admissions in children
testing positive for coronavirus (COVID-19) has been noted and summary information is
included on this. Analysis is underway to understand if this relates to Omicron and to
characterise the admissions.
Symptoms
Symptoms In NHS Test and Trace data, loss of smell or taste was reported less often by
Omicron cases than Delta cases (13% of Omicron cases, 34% of Delta cases, aOR: 0.22, 95%
CI: 0.21-0.23). Sore throat was reported more often by Omicron cases (53% of Omicron cases,
34% of Delta cases, aOR: 1.93, 95% CI: 1.88-1.98): note, however, that another recent study
observed increase in sore throat also being reported amongst those who test negative for
SARS-CoV-2 so this may be an incidental finding.
Vaccine effectiveness
In updated population data analysis, vaccine protection against mild disease has largely
disappeared by 20 weeks after vaccination with a 2-dose primary course of vaccination. After a
booster dose, protection initially increases to around 65 to 70% but drops to 45 to 50% from 10+
weeks. It is therefore likely that current vaccines offer limited long-term protection against
infection or transmission. Protection against severe disease is much higher – after a booster
dose vaccine effectiveness against hospitalisation is estimated at 92% and remains high at 83%
10+ weeks after the booster dose. This data will also appear in the weekly COVID-19 vaccine
surveillance report published routinely on a Thursday.
3
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
SIREN study
In the SIREN study, a large cohort of healthcare workers are tested regularly by polymerase
chain reaction (PCR) to detect asymptomatic infection in addition to normal testing practices for
symptomatic infection. Updated analysis shows the additional incremental benefit from each
vaccine exposure including for boosters, even in those who have had prior infection.
Updated risk assessment
An updated risk assessment for Omicron VOC-21NOV-01 (B.1.1.529) has been published.
4
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Published information on variants
The collection page gives content on variants, including prior technical briefings. Definitions for
variants of concern, variants under investigation, and signals in monitoring are detailed in
technical briefing 8.
The UK Health Security Agency (UKHSA), formerly Public Health England (PHE), has curated a
repository from 5 March 2021 containing the up-to-date genomic definitions for all VOCs and
VUIs. The repository is accessible on GitHub.
Technical briefings are published periodically. From technical briefing 15, briefings include
variant diagnoses identified by whole-genome sequencing and a genotyping polymerase chain
reaction (PCR) test, including the categorisation of sequenced and genotyped variant results
and a rules-based decision algorithm (RBDA) to identify variant and mutation (VAM) profiles
from genotype assay mutation profiles. Genotyping is used to identify variants Alpha, Beta,
Delta, Gamma and Mu. Targets were updated in mid-May 2021 to prioritise accurate
identification of Delta over Alpha.
5
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Part 1. Surveillance overview
1.1 VOC and VUI overview
Summary epidemiology for each variant and case numbers are updated online.
Figure 1 shows the cumulative number of cases per variant indexed by days since the first
report.
Figure 1. Cumulative cases in England of variants indexed by days since the fifth
reported case as of 9 January 2022
(Find accessible data used in this graph in underlying data.)
The prevalence of different variants amongst genotyped cases is presented in Figure 2. The
prevalence of different variants amongst sequenced cases is split by travel status in Figure 3.
Genotyping provides probable variant results with a shorter turnaround time of 12 to 24 hours
after initial confirmation of COVID-19 by PCR. The initial panel of targets began trials in March
2021, using single nucleotide polymorphisms that included N501Y, E484K, K417N, and K417T.
Results have been reported and used for public health action since 29 March 2021. On 11 May
2021, after rapid validation of targets to allow identification of Delta variant, P681R was
introduced in the panel to replace N501Y. The assay was further updated on 15 December
6
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34 2021 to allow improved identification of Omicron variant, with the introduction of the Q493R mutation. Genotyping results have now been fully integrated into the variant data reports and analyses. Changes in the use of genotyping over time should be considered when interpreting prevalence from genotyped data. The ‘Other’ category in Figure 2 and Figure 3 includes genomes where the quality is insufficient to determine variant status and genomes that do not meet the current definition for a VUI or VOC. The Omicron genome (lineage BA.1) contains the spike deletion at position 69-70 which is associated with S-gene target failure (SGTF) in some widely used PCR tests. Such PCR tests evaluate the presence of 3 SARS-CoV-2 genes: Spike (S), N and ORF1ab. SGTF is defined as a PCR test where the N and ORF1ab genes are detected (with Ct values
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 2. Variant prevalence for all England available genotyped cases from 1 February 2021 as of 10 January 2022
(Find accessible data used in this graph in underlying data.)
8
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 3. Prevalence of variants over time: all sequenced cases in England, split by travel status as of 10 January 2022
(excluding 1,001 cases where the travel status or specimen date were unknown)
(Find accessible data used in this graph in underlying data.)
9
SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 4. Number of COVID-19 cases with S-gene positive/SGTF by day, among those tested in TaqPath labs as of 10 January
2022 (95% confidence intervals indicated by grey shading. Percentages for most recent 7 days shown)
10SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
(Find accessible data used in this graph in underlying data.)
11SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 5. Prevalence of Pangolin lineages in UK with sequence data from 1 April 2021 to 11 January 2022
The total number of valid sequence results per week is shown by the black line. Only lineages with more than 5,000 sequences are shown.
Smaller lineages are either merged with parent lineages (for example, AY.3.1 is included in AY.3) or are included in ‘Other’.
(Find accessible data used in this graph in underlying data.)
12SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
13SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Part 2. Enhanced analyses of Omicron VOC-
21NOV-01 (B.1.1.529)
A new variant with a novel combination of mutations was detected on GISAID on 23 November
2021 and designated B.1.1.529 on 24 November 2021. This variant was designated VUI-
21NOV-01 by the UKHSA Variant Technical Group and on review re-designated as VOC-
21NOV-01 on 27 November 2021.
2.1 Genomic diversity
Spike mutations are monitored within BA.1 using 4 criteria (Table 1). A mutation is investigated
further if it meets more than one of these criteria and is present in at least 10 sequences.
Fifteen additional mutations have been observed in BA.1 sequences according to the criteria in
Table 2 (Figure 6). However, L452R is observed in sequences that are suspected to have a low
level of contamination. This Delta mutation is observed because amplicon 76 of the Artic V4
primers is not amplified in Omicron genomes due to mutations across the primer site. Therefore,
the expected Omicron mutations are not observed in these sequences, and L452R is present in
contaminating Delta reads. The mutation N211S is an alignment artifact caused by the deletion
at this position in Spike. The deletion is also the reason that N211S appears to be such a high
proportion, despite being a low number of total sequences, as the amino acid at position 211
cannot be called in most Omicron genomes therefore reducing the total number of sequences
used to calculate the proportion.
Table 1. Criteria used to assess emerging mutations
Criteria Threshold
Cumulative count Running total for the number of sequences containing
mutation is at least 50
Proportion 1% of sequences classified as this variant contain this
mutation within a single week
Difference in proportion The difference in the proportion of sequences in 2
consecutive weeks is at least 0.25%
Percentage change in the The percentage change between the number of sequences
number of sequences containing the mutation in 2 consecutive weeks is at least 5%
14SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 6. Proportion of sequences containing a given mutation within UK BA.1
sequences that meet more than one criterion and are present in at least 10 sequences
Data shown is sequence data from 6 September 2021 to 9 January 2022. Nine sequences were
excluded due to metadata issues. The proportion of sequences is indicated by the colour and
the number of genomes is shown within the tile. Proportion is calculated based on the total
number of sequences where the amino acid can be called. Mutations expected to be in all
Omicron genomes are shown separately to those considered to have been acquired since initial
emergence of the lineage. The total number of sequences per week is shown by the black line
in the lower plot.
15SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Growth rates for mutations occurring on Omicron
As Omicron the growth of variants with each mutation, relative to variants that do not have each
mutation, is estimated. The growth rate is estimated by logistic regression of the number of
variants with the mutation on the time of sample collection. Sample inclusion criteria are:
a non-traveller as determined by matching each case against passenger locator forms
and managed quarantine service test codes; collected from Pillar 2 testing. A growth
rate of 0 would indicate parity with variants that do not have the mutation.
16SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Data sampled up to 31 December 2021 were included, and the following Spike mutations were
evaluated: E309K, R346K, A701V, D1048E, I1081V, V1264M. None of these mutations have
increased significantly since the introduction of Omicron. The relative proportions through time
and the growth rate of the 2 most frequent mutations R346K (n=5,415) and A701 (n=15,438),
are displayed in Figure 7.
Figure 7. Sample frequency and growth rates for spike mutations A701V and R346K, as
compared to Omicron sequences that do not have each mutation.
There is no supplementary data for this figure.
17SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
BA.2
This variant is a sub-lineage of Omicron (VOC-21NOV-01) that was designated by Pangolin on
6 December 2021. This sub-lineage does not have the spike gene deletion at 69-70 that causes
SGTF. An increase in the number of sequences of the Omicron sub-lineage BA.2 was noted
from both the United Kingdom (UK) and Denmark in the week starting the 3 January 2022. The
spike profile of BA.2 contains 28 mutations and a deletion at 25-27. The comparison of the
Omicron sub-lineages was previously reported in Technical Briefing 31 (Figures 9 and 10).
Epidemiology
As of 10 January 2022, 53 sequences of BA.2 have been identified in the UK. BA.2 accounts for
an increasing proportion of S-gene positive (SGTP) tests. Therefore, caution is required when
interpreting comparative analyses which use S-gene target results as the only determinant of
Omicron and Delta.
International epidemiology
18SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
As of 10 January 2022, 2,093 sequences on GISAID meet the Omicron BA.2 Pangolin definition
from 22 countries including the UK (Figure 8). Figure 8 shows an increasing number of BA.2
sequences in recent weeks, many from Denmark. The most recent week will be affected by
data lags.
Figure 8. Count of Omicron BA.2 classified sequences by week of collection uploaded to
GISAID by week as of 10 January 2022
Countries with 10 or fewer sequences have been grouped together as ‘Other’. (Find accessible
data used in this graph in underlying data)
19SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
2.2 Severity and hospitalisation
Descriptive epidemiology of severe outcomes of Omicron in England
Cases, hospitalisation, attendance and deaths by vaccination status are now presented in the
COVID-19 vaccine surveillance report.
Analyses on the risk of hospitalisation were reported in Technical Briefing 33. These analyses
indicated that relative to Delta, the risk of hospitalisation following infection with Omicron is
lower in adults. Studies to further investigate the severity of Omicron infection compared to
Delta are underway.
Paediatric infections and admissions
Hospital admission data is reported by NHS England and Improvement and include people
admitted to hospital who either tested positive for COVID-19 during their admission or in the
previous 14 days before their admission.
The number of paediatric admissions with COVID-19 infection began to rise from 26 December
2021, from an average of 40 admissions per day to 120 per day, a 3-fold rise in 2 weeks.
Further analysis by age group shows that the rise is most rapid among children under 5 years,
and highest in infants aged under 1 year (Figure 9). This data is for all COVID-19 infections
including all variants, but it should be noted that Omicron represented over 90% of sequenced
samples in the UK from end November 2021 (Figure 5). The top 3 complaints on hospital
attendance records for children under 5 remain consistent with respiratory infection.
A clinical case review of a small number of Omicron admissions in infants found those admitted
were not severely unwell. The Royal College of Paediatrics and Child Health (RCPCH) has
issued a statement to confirm that paediatricians are not reporting Omicron to be a more
serious or severe disease in children and young people in the UK.
20SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 9. Rolling 7-day average number of children and young people admitted to
hospital with COVID-19, 7 January 2021 to 9 January 2022
(Source: NHS England and Improvement/GOV.UK Dashboard)
2.4 Symptom comparison of Omicron and Delta
cases in England
This section contains an analysis exploring the difference in symptoms reported to NHS Test
and Trace of sequenced or genotyped confirmed Omicron and Delta cases for the period 1
December to 28 December 2021.
Symptomatic cases represented 89.8% of all Omicron cases and 85.5% of all Delta cases who
completed contact tracing. It should be noted that this dataset is affected by testing behaviours
and contact tracing engagement and should not be used to assess the asymptomatic fraction.
Analysis was based on 182,133 Omicron and 87,920 Delta cases reporting symptoms with
onset in this period that had completed contract tracing and reported symptoms, and had
provided data on their age, sex and region.
Confirmed cases were asked if they displayed any of the following symptoms: fever, cough,
shortness of breath, fatigue, altered consciousness, muscle or joint pain, headache, loss of
smell or taste, sore throat, runny nose, sneezing, rash, red or irritated eye, loss of appetite,
21SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
nausea or vomiting, or diarrhoea. The median number of reported symptoms per case in this
cohort was equal between variants (Median: 4.0, interquartile range (IQR): 2.0 – 6.0). Time
taken between symptom onset and completing contact tracing was slightly longer for Omicron
cases (Median: 3.9 days, IQR: 2.2-5.1) compared to Delta (Median: 3.1 days, IQR: 2.0-4.9)
cases.
Odds ratio analysis compared the odds of a specific symptom being reported by an Omicron or
a Delta case whilst adjusted odds ratio analysis compared the odds of a specific symptom being
reported by an Omicron or a Delta case whilst adjusting for age group, sex, ethnicity, self-
reported vaccination status (two or more doses, one or no dose, or missing data), geographical
region of residence, and the week in which symptoms began.
Figure 10 shows a forest plot of adjusted odds ratios of symptoms being reported by Omicron
cases compared to Delta cases. Sore throat was more likely to be reported by cases with
Omicron (53% of Omicron cases, 34% of Delta cases, odds ratio 1.93, 95% CI: 1.88-1.98). On
the other hand, loss of smell and taste was found to be less common among Omicron
compared to Delta cases (13% of Omicron cases, 34% of Delta cases, odds ratio 0.22, 95% CI:
0.21-0.23).
A recent study led by Oxford University and the Office for National Statistics studied symptoms
reported by PCR-positive and PCR-negative individuals using data from the UK Covid-19
Infection Survey. As Omicron cases increased as a proportion of SARS-CoV-2 infections during
December 2021, the study found increased reports of sore throat and a marked reduction in
reporting of loss of smell and taste in PCR-positives. This study also found that sore throat
became more commonly reported in symptomatic PCR-negative cases during this period,
suggesting that sore throat may not be a specific predictor of SARS-CoV-2 infection with
Omicron.
Important limitations of this analysis:
• negative COVID-19 test results were not included in this dataset, and therefore
differences between symptoms in people testing negative and positive could not be
compared; no conclusions can be drawn about the specificity of these symptoms as
indicators of SARS-CoV-2 infection
• symptom data was collected at the time of contact tracing only (usually 3-4 days post
symptom onset), and therefore additional symptoms presenting at a later timepoint
are not captured
• any changes in testing behaviour during the month of December may also affect the
results
• vaccination data used for adjustment is self-reported to NHS Test and Trace and
does not include information on booster doses
22SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 10. Forest plot of adjusted* odds ratios of specific symptoms reported amongst
Omicron vs Delta cases
Cases with symptom onset 1 December to 28 December 2021, transferred to NHS Test and
Trace by 31 December 2021. Variant data as of 3 January 2022 and contact tracing data as of
11 January 2022.
* Odds ratios adjusted for age group, sex, ethnicity, self-reported vaccination status (2 or more
doses, one or no dose, or missing data), geographical region of residence, and the week in
which symptoms began
Note: Trends from crude analysis may differ from those in adjusted analysis due to differences
in demographic and other characteristics between cases with each of the variants.
23SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
2.5 Vaccine effectiveness
A test negative case control design was used to estimate vaccine effectiveness (VE) against
symptomatic COVID-19 with the Omicron variant compared to the Delta variant. Here
vaccination rates in PCR positive cases are compared to vaccination rates in those who test
negative. Individuals who reported symptoms and tested in Pillar 2 (community testing) between
27 November 2021 and 6 January 2022 were included in the analysis.
Cases were defined as the Omicron variant or Delta variant based on whole genome
sequencing, genotyping or S-gene target status on PCR testing. The Omicron variant has been
associated with a negative S-gene target result on PCR testing with the TaqPath assay
whereas with the Delta variant the S-gene target is almost always positive. Vaccine
effectiveness was estimated by period after dose 2 and dose 3. Results are presented for 18+
year olds.
Pillar 2 symptomatic confirmed cases were linked to the Emergency Care Data Set (ECDS) to
identify admissions via emergency care 0 to 14 days after the positive test (excluding
admissions due to injuries). Cox survival analysis was then used to estimate the risk of hospital
admission by vaccination status. Due to small numbers all vaccine brands are considered
together. Adjustments were made or age, gender, previous positive test, region, ethnicity, travel
history, clinically extremely vulnerable status, risk group status and period. To estimate vaccine
effectiveness against hospitalisation the odds ratios (OR) for symptomatic disease were
multiplied by the hazards ratios (HR) for hospitalisation among symptomatic cases:
VEhospitalisation = 1-(ORsymptomatic disease x HRhospitalisation).
The symptomatic disease test negative case control analysis included 236,023 Delta cases and
760,647 Omicron cases. Vaccine effectiveness against symptomatic disease by period after
dose 2 and dose 3 is shown in Figure 11 for those who received a primary course of the
AstraZeneca vaccine (Figure 11a), Pfizer (Figure 11b) or Moderna (Figure 11c). Effectiveness
of booster doses of Pfizer and Moderna are shown. In all periods, effectiveness was lower for
Omicron compared to Delta. Among those who had received 2 doses of AstraZeneca,
effectiveness dropped from 45 to 50% to almost no effect against Omicron from 20 weeks after
the second dose. Among those who had received 2 doses of Pfizer or Moderna effectiveness
dropped from around 65 to 70% down to around 10% by 20 weeks after the 2nd dose. Two to 4
weeks after a booster dose vaccine effectiveness ranged from around 65 to 75%, dropping to
55 to 65% at 5 to 9 weeks and 45 to 50% from 10+ weeks after the booster.
24SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 11. Vaccine effectiveness against symptomatic diseases by period after dose 1
and dose 2 for Delta (black squares) and Omicron (grey circles) for (a) recipients of 2
doses of AstraZeneca (ChAdOx1-S) vaccine as the primary course and Pfizer (BNT162b2)
or Moderna (mRNA-1273) as a booster; (b) recipients of 2 doses of Pfizer vaccine as the
primary course and Pfizer or Moderna as a booster, and (c) recipients of 2 doses of
Moderna as a primary course (insufficient data for boosters after a Moderna primary
course)
Supplementary data is not available for this figure.
(a)
25SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
(b)
(c)
26SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Results for hospitalisations are shown in Table 2. One dose of vaccine was associated with a
43% reduced risk of hospitalisation among symptomatic cases with the Omicron variant, 2
doses with a 55% reduction up to 24 weeks after the second dose and a 40% reduced risk 25 or
more weeks after the second dose, and a third dose was associated with a 74% reduced risk of
hospitalisation in the first 2 to 4 weeks after vaccination, dropping slightly to a 66% reduction by
10+ weeks after the booster dose. When combined with vaccine effectiveness against
symptomatic disease this was equivalent to vaccine effectiveness against hospitalisation of 58%
after one dose, 64% 2 to 24 weeks after 2 doses, 44% 25+ weeks after 2 doses, and 92%
dropping to 83% 10+ weeks after a booster dose. Combining the periods for the third dose,
overall vaccine effectiveness 2+ weeks after the booster was 89% (95% confidence interval 86
to 91%).
Table 2. Hazard ratios and vaccine effectiveness against hospitalisation (all vaccine
brands combined). OR = odds ratio, HR = hazards ratio, VE = vaccine effectiveness
Dose Interval after OR v symptomatic HR vs VE vs
dose (weeks) disease hospitalisation hospitalisation
1 4+ 0.74 (0.72-0.76) 0.57 (0.38-0.85) 58% (37-72)
2 2 to 24 0.81 (0.8-0.82) 0.45 (0.36-0.56) 64% (54-71)
2 25+ 0.94 (0.92-0.95) 0.6 (0.49-0.74) 44% (30-54)
3 2 to 4 0.32 (0.31-0.33) 0.26 (0.19-0.35) 92% (89-94)
3 5 to 9 0.42 (0.41-0.43) 0.29 (0.23-0.37) 88% (84-91)
3 10+ 0.5 (0.49-0.51) 0.34 (0.26-0.44) 83% (78-87)
These estimates suggest that vaccine effectiveness against symptomatic disease with the
Omicron variant is significantly lower than compared to the Delta variant and wane rapidly.
Nevertheless, protection against hospitalisation is much greater, in particular after a booster
dose, where vaccine effectiveness against hospitalisation is around 85 to 90%. Further data is
needed to estimate the duration of protection against hospitalisation.
27SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
2.6 Update on the SARS-CoV-2 Immunity and
Reinfection Evaluation in healthcare workers
(SIREN) study
The SIREN study is a cohort of over 44,000 National Health Service healthcare workers,
recruited from 135 hospital sites UK-wide. Participants under active follow-up undergo
asymptomatic SARS-CoV-2 PCR testing every 2 weeks. This cohort had high seropositivity on
recruitment (30% before the second wave) and is now highly vaccinated (>95%). The incidence
of new infections and potential reinfections in SIREN is monitored.
Figure 12 describes fortnightly trends in primary PCR positivity and number of participants
tested within the SIREN study from 15 June 2020 to 9 January 2022. Since mid-December
2021, there has been a steep increase in the PCR positivity, which continues to increase over
the last 2 time periods.
Figure 12. Fortnightly trends in primary PCR positivity and number of participants tested
within the SIREN study from 15 June 2020 to 9 January 2022
Supplementary data is not available for this figure.
90 35000
Participants PCR tested within period
80
Participants with positive PCR test
30000
70
within period (per 1,000)
25000
60
50 20000
40 15000
30
10000
20
5000
10
0 0
15 13 10 07 05 02 30 28 25 22 22 19 17 14 12 09 06 04 01 29 27
Jun Jul Aug Sep Oct Nov Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Nov Dec
14 days beginning
Notes: Data is preliminary and undergoing review. Data at the latest timepoint may be affected
by delayed reporting.
28SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 13 shows the counts of reinfection over fortnightly time periods. Reinfections were
defined as new PCR positive infections 90 days after a previous PCR positive date or 28 days
after antibody positivity consistent with prior infection. The number of reinfections has also
rapidly increased over a similar time period as the primary infections (Figure 12), since mid-
December 2021 to date.
Figure 13. Number of reinfections in SIREN participants in the UK from 15 June 2020 to 9
January 2022
Supplementary data is not available for this figure.
250
Number of reinfections among SIREN
200
150
participants
100
50
0
15 13 10 07 05 02 30 28 25 22 22 19 17 14 12 09 06 04 01 29 27
Jun Jul Aug Sep Oct Nov Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Nov Dec
14 days beginning
Notes: Data is preliminary, and includes all possible reinfections flagged, but some may
subsequently be excluded following clinical review. Data at the latest timepoint may be affected
by delayed reporting.
We have conducted a rapid preliminary assessment of protection from Omicron infections
(including symptomatic and asymptomatic infections) provided by COVID-19 vaccination and
prior SARS-CoV-2 infection in the SIREN cohort between 1 December 2020 and 4 January
2022. We restricted our analysis to 18,464 participants remaining under active follow-up during
this period. Participants were categorised by vaccination and prior infection status on 30
November 2021. End of follow-up for individual participants was either event date or date of last
negative PCR test up to 4 January 2022. The outcome of interest was a PCR positive primary
infection or reinfection (symptomatic and asymptomatic). Reinfections were defined as new
PCR positive infections 90 days after a previous PCR positive date or 28 days after antibody
positivity consistent with prior infection. Incidence Rate Ratios (IRR) were estimated using a
Poisson regression model. These are preliminary estimates and do not account for other
factors, including time since vaccination and variable baseline hazards (such as incidence of
infections) during this period. It would be anticipated that after accounting for the non-constant
hazards the VE estimates for dose 3 would be slightly higher than those presented from this
constant hazards analysis.
29SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
By 30 November 2021 11,084 (60%) participants had no previous SARS-CoV-2 infection and
6,974 (40%) participants had prior infection, and most had received 3 doses of COVID-19
vaccine, primarily the BNT162b2 mRNA vaccine.
The results show the increased protective effect of a booster dose of the COVID-19 vaccine,
even in those with prior infection, against symptomatic and asymptomatic Omicron infections
compared to uninfected unvaccinated participants, who experienced the highest infection risk
(table 3). There is an additional incremental benefit from each vaccine exposure, even in those
who have had prior infection (confirmed through antibody or detection through asymptomatic
and symptomatic testing). This is an early unadjusted output with uncertainty in the estimates
which will be iterated and refined in future analyses.
30SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Table 3. Incidence of Omicron infections in the SIREN cohort between 1 December 2021 and 4 January 2022 by vaccination
and prior infection status on 30 November 2021 (n=18,464)
Number of Crude incidence Vaccine
Number of Number of
Status days of rate (per 10,000 effectiveness (%) 95% CI
participants infections
follow up person days) (100 x1-IRR)
No previous infection and vaccine status on 30 November 2021
Unvaccinated 87 1,935 21 108.5 Ref Ref
Vaccinated 2 dose 1,156 24,801 182 73.4 32% -6%-57%
Vaccinated 3 dose 9,841 225,126 937 41.6 62% 41%-75%
Prior infection and vaccine status on 30 November 2021
Unvaccinated 255 5,750 35 60.9 44% 4%-67%
Vaccinated 2 dose 1,333 28,255 123 43.5 60% 36%-75%
Vaccinated 3 dose 5,386 121,762 377 31.0 71% 56%-82%
Notes: IRR Incidence Rate Ratios. IRR are not adjusted.
31SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
2.7 Reinfections
Cases of reinfection (at any interval) extracted on 8 January 2022 were identified amongst all
SARS-CoV-2 positive cases in England. As Omicron now accounts for almost all SARS-CoV-2
infection, cases of possible reinfection (an interval between 2 sequential positive SARS-CoV-2
test results of >=90 days) with the Omicron variant are no longer being distinguished. Details on
overall reinfections are being published weekly in the UKHSA National flu and COVID-19
surveillance reports through January. Provisional data for week 2021-52 (beginning 27
December 2021) identified 106,297 possible reinfections accounting for 9.5% of all infections
that week.
Reinfection rates are usually generated using the population of previous infections eligible to
become a reinfection (that is with a previous positive test result at least 13 weeks (>90 days)
earlier). Using this as a measure of current reinfection rates in the population there is now a
marked increase in overall reinfection rates, this is disproportionate to the increase in first
infections.
The overall age distribution of possible Omicron reinfections with an interval of at least 90 days
since the previous episode closely follows the overall distribution of first infections by Omicron
through the same time period (confirmed or probable cases in England 1 November to 30
December 2021), Figure 14.
32SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 14. Age profile of first episodes of infection and possible reinfection (90+ day interval between sequential positive test
results) with Omicron (1 November to 30 December 2021)
Supplementary data is not available for this figure.
For possible reinfections with a shorter interval between previous infection and confirmed/probable infection with Omicron at 60 to 89
days later, the highest possible reinfection case numbers have been seen in the secondary school age group. This closely follows the
age distribution of first episodes in September/October (Figure 15) which means individuals in this age group are the most likely to fit
possible reinfection criteria with a shorter interval. The age distribution of cases of possible reinfection with Omicron at 29 to 59 days
after a previous infection also reflects the raised numbers of first positive tests in the school age groups through September/ October
33SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
2021 but is less well-defined in older ages (Figure 16), possibly as there is an increased likelihood of persistent detection of virus in this
shorter interval.
Figure 15. Age profile of first episodes of infection (September to October 2021) and possible reinfections with Omicron
(1 November to 30 December 2021) with a 60-to-89-day interval between Omicron positive test result and previous
positive test
Supplementary data is not available for this figure.
34SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Figure 16. Age profile of first episodes of infection (September to October 2021) and possible reinfections with Omicron
(1 November to 30 December 2021) with a 29-to-59-day interval between Omicron positive test result and previous
positive test
Supplementary data is not available for this figure.
35SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
36SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Sources and acknowledgments
Data sources
Data used in this investigation is derived from the COG-UK and UKHSA genomic programme
data set, the UKHSA Second Generation Surveillance System (SGSS), the Secondary Uses
Service (SUS) data set, Emergency Care Data Set (ECDS), the UKHSA Case and Incident
Management System (CIMS), and the SARS-CoV-2 Immunity and Reinfection Evaluation
(SIREN) Study.
Repository of human and machine-readable
genomic case definitions
Genomic definitions for all VOC and VUI are provided in order to facilitate standardised VOC
and VUI calling across sequencing sites and bioinformatics pipelines and are the same
definitions used internally at UKHSA. Definition files are provided in YAML format so are
compatible with a range of computational platforms. The repository will be regularly updated.
The genomic and biological profiles of VOC and VUI are also detailed on first description in prior
technical briefings.
Authors of this report
UKHSA Genomics Cell
UKHSA Outbreak Surveillance Team
UKHSA Epidemiology Cell
UKHSA Immunisations Team
UKHSA Contact Tracing Data Team
UKHSA Environmental Monitoring for Health Protection Team
UKHSA SIREN Study Team
UKHSA Public Health Incident Directors
Contributions from the Variant Technical Group Members
37SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Variant Technical Group members
Person Institution
Meera Chand (chair) UKHSA
Genomics and bioinformatics
Andrew Rambaut University of Edinburgh
Nicholas Loman UKHSA/University of Birmingham
Richard Myers UKHSA
Jeffrey Barrett Wellcome Sanger Institute
Matt Holden Public Health Scotland
Virology and Immunology
Wendy Barclay Imperial College London
Gavin Screaton University of Oxford
Maria Zambon UKHSA
Paul Kellam Imperial College London
Kevin Brown UKHSA
Susanna Dunachie University of Oxford
Lance Turtle University of Liverpool
Ravi Gupta University of Cambridge
Bassam Hallis UKHSA
Tim Wyatt Northern Ireland Public Health Agency
Thomas Peacock Imperial College London
Thushan da Silva University of Sheffield
Epidemiology and modelling
Susan Hopkins UKHSA
Jamie Lopez-Bernal UKHSA
Simon Thelwall UKHSA
Thomas Finnie UKHSA
Richard Elson UKHSA
Charlotte Anderson UKHSA
Erik Volz Imperial College London
John Edmunds London School of Hygiene and Tropical Medicine
Neil Ferguson Imperial College London
Daniela de Angelis University of Cambridge
38SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34
Person Institution
Maria Rossi Public Health Scotland
Chris Williams Public Health Wales
Anna Seale UKHSA/University of Warwick
Julia Gog SPI-M / University of Cambridge
International epidemiology
Katherine Russell UKHSA
Chris Lewis Foreign, Commonwealth and Development Office
Leena Inamdar UKHSA
The UK Health Security Agency Variant Technical Group includes members and contributors
from the following organisations: UKHSA, Public Health Wales, Public Health Scotland, Public
Health Agency Northern Ireland, the Department of Health and Social Care, Imperial College
London, London School of Hygiene and Tropical Medicine, University of Birmingham, University
of Cambridge (including the MRC Biostatistics Unit), University of Edinburgh, University of
Liverpool, the Wellcome Sanger Institute, Genotype to Phenotype Consortium, SPI-M.
Acknowledgements
The authors are grateful to those teams and groups providing data for these analyses including:
the Lighthouse Laboratories, NHS, COG-UK, the Wellcome Sanger Institute, Health Protection
Data Science teams, the University of Oxford, the Genotype to Phenotype Consortium and the
SIREN study.
39About the UK Health Security Agency
UKHSA is responsible for protecting every member of every community from the impact of
infectious diseases, chemical, biological, radiological and nuclear incidents and other health
threats. We provide intellectual, scientific and operational leadership at national and local
level, as well as on the global stage, to make the nation health secure.
UKHSA is an executive agency, sponsored by the Department of Health and Social Care.
© Crown copyright 2022
Version 1.0
Published: January 2022
Publishing reference: GOV-10924
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